Background

Pasteurella multocida is a small, gram-negative, nonmotile, non–spore-forming coccobacillus with bipolar staining features. The bacteria typically appear as single bacilli on Gram stain; however, pairs and short chains can also be seen. P multocida often exists as a commensal in the upper respiratory tracts of many livestock, poultry, and domestic pet species, especially cats and dogs. In fact, Pasteurella species are some of the most prevalent commensal bacteria present in domestic and wild animals worldwide. P multocida infection in humans is often associated with an animal bite, scratch, or lick, but infection without epidemiologic evidence of animal contact may occur. See the image below.

View Image

Pasteurella multocida infection.

Wound infections associated with animal bites usually have a polymicrobial etiology, mandating the empiric use of broad-spectrum antimicrobials targeted at both aerobic and anaerobic gram-negative bacteria. Nevertheless, Pasteurella species are commonly isolated pathogens in most animal bites, especially in dog- and cat-related injuries. These injuries can be aggressive, with skin manifestations typically appearing within 24 hours following a bite. These wounds can exhibit a rapidly progressive soft-tissue inflammation that may resemble group A β-hemolytic Streptococcus pyogenes infections.

Deeper soft tissue can also be affected, manifesting as tenosynovitis, septic arthritis, and osteomyelitis. More-severe disseminating infections may also develop, including endocarditis or meningitis, the latter mimicking Haemophilus influenzae or Neisseria meningitides infections in young children. Fortunately, Pasteurella species are fairly sensitive organisms and can be treated with a penicillin-based regimen.

Pathophysiology

Local: P multocida infection usually presents as an infection that complicates an animal bite or injury. Complications include rapidly progressive cellulitis, abscesses, tenosynovitis, osteomyelitis, and septic arthritis.[1] The latter two are particularly common following cat bites because of their small, sharp, penetrative teeth.[2]

Central nervous system: P multocida is an uncommon cause of meningitis,[13] subdural empyema, and brain abscess.[14] P multocida meningitis has been associated with cat licks and bites occurring on the face in persons at the extremes of age.[15]

Epidemiology

Frequency

United States

According to the American Pet Products Association, approximately 180 million dogs and cats live in the United States, cats currently outnumbering dogs by 12 million. Animal bites account for 1% (300,000) of annual emergency department visits. The estimated cost in health care expenditures has been reported to be $30 million per year. Approximately 10% of animal bites require medical attention; 1-2% eventually require hospitalization.

Approximately 5 million animal bites are reported annually. The vast majority of animal bites involve dogs (85-90%), followed by cats (5-10%).

Infectious complications occur in approximately 15-20% of dog-related bites and more than 50% of cat-related ones. Dog bites are associated with younger animals engaging in playful activities, mostly with children. German shepherd, pit bull, Staffordshire terrier, and mixed breeds are most commonly involved with human bites, while the golden retriever and Labrador retriever are least. Cat bites are usually provoked, typically by female felines, and occurring on the upper extremities or face. Sharp and long teeth of cats can easily penetrate human skin and create a deep puncture wound and even inoculate the periosteum component of bones. Indeed, cat-related wounds more commonly progress to more serious and deeper-tissue infections, including osteomyelitis and meningitis.

Mortality/Morbidity

It is estimated that 10-20 human deaths per year occur following an animal bite.

Infectious complications occur in approximately 15-20% of dog-related bites and more than 50% of cat-related ones. Following a bite, a rapidly progressive cellulitis may develop; deeper structures, including tendons, joints, and bones, can become affected, especially in cat-related injuries. Dissemination can occur.

Degenerative joint disease, rheumatoid arthritis, and prosthetic joints have been associated with the development of P multocida septic arthritis.[18]

Chronic obstructive pulmonary disease is a risk factor for P multocida respiratory tract infection,[19] which carries a mortality rate of approximately 30%. Diabetes mellitus[20] and liver dysfunction[21] are predisposing conditions associated with pasteurellosis and associated bacteremia.

P multocida infections during pregnancy and in utero transmission have also been reported.[22, 23, 24]

Age

All age groups can be affected by P multocida infections. Young children seem to be frequently involved in nonfatal dog bites. P multocida meningitis typically occurs in persons at the extremes of age.

History

A history of animal exposure, whether occupational or recreational, should alert the physician to the possibility of a zoonosis.[25]

A detailed pet history, including exposure to pets owned by friends or strangers, should reveal the possibility of Pasteurella infection. However, cases of Pasteurella infection occur in the total absence of an epidemiological link.

Laboratory Studies

Gram stain of purulent material or other fluid specimens including blood, sputum, and cerebrospinal fluid may show small, gram-negative, nonmotile, non–spore-forming pleomorphic coccobacilli.

Haemophilus species, N meningitides, Moraxella species, and Acinetobacter species have a morphology that is similar to that of P multocida infection and can therefore be easily confused with Pasteurella species .

Pasteurella species are highly sensitive to several penicillins and cephalosporins. Susceptibility testing is indicated in immunocompromised patients and in the setting of treatment failure or drug allergies.

Procedures

Deep soft-tissue P multocida infections require debridement at times. Intraoperative cultures should be taken at time of surgery.

Lumbar puncture should be performed if meningitis is suspected.

Arthrocentesis should be performed if septic arthritis is suspected.

Abdominal paracentesis is required in patients with ascites to assess the possibility of spontaneous bacterial peritonitis, especially in those with significant clinical liver disease with a history of pet exposure.

Histologic Findings

Medical Care

Because P multocida infection is mostly encountered in the setting of an injury following an animal bite, physicians must be familiar with the associated microbiological oral flora of certain animals, especially dogs and cats.

Most animal bites are polymicrobial, with both aerobic and anaerobic bacteria. Several species can be isolated at once.

Several Pasteurella species are associated with dog and cat bites, including P multocida subspecies multocida,P multocida subspecies septica, Pasteurella stomatis, and Pasteurelladogmatis. Pasteurella canis is associated only with dog bites.

Other fastidious gram-negative organisms that have been associated with dog and cat bites include Capnocytophaga canimorsus and Capnocytophaga cynodegmi, especially in patients who had undergone previous splenectomy. C canimorsus infection can cause fulminant sepsis and meningitis, whereas C cynodegmi infection usually causes a milder localized inflammation.

Several other organisms are associated with cat bites, including Bartonella henselae, Francisella tularensis, and cowpox virus.

Local care of bite wounds includes cleansing and removing nonviable tissue. Gently cleanse the skin surrounding the bite wound with an antiseptic solution. To prevent further tissue injury, do not scrub the wound directly. Soaking is of no benefit, but copious irrigation with a small-gauge catheter on a syringe helps remove debris and decreases the concentration of bacteria in contaminated wounds. Debridement and closure are discussed in Surgical Care.

Surgical Care

The initial assessment of an animal bite includes an estimation of the infection risk. Bites to the head and neck, to the distal extremities, and near joints carry the highest risk of infection. In general, persons with animal bite wounds are at a high risk for infection, especially those who present to medical attention more than 8-10 hours after the injury occurred.

Consultations

Activity

Elevation is of great importance in the management of limb injuries. Lack of elevation may result in excessive edema, which may produce compartment syndrome and compromise local circulation, to the extent of threatening the viability of the limb.

Wounds on extremities should be immobilized and elevated with a sling to reduce edema, which may hamper normal activities.

Medication Summary

Antimicrobial resistance among Pasteurella isolates is rarely reported in humans. Tetracyclines, erythromycin, and penicillin are most commonly associated with resistance. Penicillin-resistant strains have been isolated only from respiratory tract infections. Most animal-bite injuries can be treated with oral antimicrobials on an outpatient basis. Severe or partially responding infections may necessitate hospitalization and parenteral antimicrobial administration, along with surgical intervention.

Most Pasteurella isolates are susceptible to oral antimicrobials such as amoxicillin, amoxicillin/clavulanic acid, minocycline, fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin), and trimethoprim-sulfamethoxazole. Based on in vitro susceptibility data, several antimicrobials should not be used empirically for P multocida infections, including dicloxacillin, vancomycin, cephalexin, cefaclor, cefadroxil, erythromycin, and clindamycin. Macrolide resistance is usually encountered with erythromycin. Other macrolides, including azithromycin, clarithromycin, and telithromycin (in order of decreasing susceptibility), retain in vitro activity against most Pasteurella strains. Aminoglycosides have poor activity against P multocida.

More-severe infections may require parenteral antibiotics. Intravenous ampicillin-sulbactam, ticarcillin-clavulanate, piperacillin-tazobactam, cefoxitin, and carbapenems (imipenem-cilastatin, meropenem, ertapenem) are excellent empiric options for animal-bite injuries, providing gram-positive, gram-negative, and anaerobic coverage. The new tetracycline-derivative tigecycline also has excellent in vitro activity against P multocida and other pathogens encountered in animal and bite injuries. If P multocida is the only isolated organism, therapy may be changed to intravenous penicillin G. Once clinical improvement is noted, oral penicillin VK is an option. Patients with penicillin allergies can receive minocycline, doxycycline, fluoroquinolones, trimethoprim-sulfamethoxazole, or azithromycin.

The duration of therapy for P multocida infections has not been well established and can be tailored to clinical response. Milder soft-tissue infections usually require 7-10 days of oral therapy. More-severe cases can be treated for 10-14 days. Deep-tissue infections often require 4-6 weeks of treatment, usually with intravenous therapy initially.

Penicillin G (Pfizerpen)

Clinical Context:
Inhibits biosynthesis of cell wall mucopeptide. Bactericidal against sensitive organisms when adequate concentrations are reached. Most effective during the stage of active multiplication. Inadequate concentrations may produce only bacteriostatic effects. Use penicillin VK for PO or penicillin G for IV.

Ticarcillin and clavulanate (Timentin)

Clinical Context:
Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active growth. Antipseudomonal penicillin plus beta-lactamase inhibitor that provides coverage against most gram-positive organisms, most gram-negative organisms, and most anaerobes.

Piperacillin and tazobactam sodium (Zosyn)

Ertapenem (Invanz)

Clinical Context:
Bactericidal activity results from inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin-binding proteins. Stable against hydrolysis by various beta-lactamases including penicillinases, cephalosporinases, and extended-spectrum beta-lactamases. Hydrolyzed by metallo-beta-lactamases.

Cefoxitin (Mefoxin)

Clinical Context:
Second-generation cephalosporin with activity against some gram-positive cocci, gram-negative rod infections, and anaerobic bacteria. Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins; inhibits final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death.

Infections caused by cephalosporin- or penicillin-resistant gram-negative bacteria may respond to cefoxitin.

Concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.

Further Outpatient Care

Complications

Abscesses and tenosynovitis are the most common complications of P multocida soft-tissue infection. Septic arthritis and osteomyelitis are less common. CNS involvement with meningitis can occur. Dissemination is rare.

Chief Editor

Michael Stuart Bronze, MD, David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Larry I Lutwick, MD, FACP, Editor-in-Chief, ID Cases; Moderator, Program for Monitoring Emerging Diseases; Adjunct Professor of Medicine, State University of New York Downstate College of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

J Robert Cantey, MD Professor, Department of Medicine, Division of Infectious Diseases, Medical University of South Carolina

J Robert Cantey, MD is a member of the following medical societies: Alpha Omega Alpha, American Society for Clinical Investigation, American Society for Microbiology, Infectious Diseases Society of America, International Society of Travel Medicine, Musculoskeletal Infection Society, Phi Beta Kappa, and Southern Society for Clinical Investigation

Alexandre Lacasse, MD, MSc is a member of the following medical societies: American College of Physicians, American Medical Association, Association of Program Directors in Internal Medicine, Infectious Diseases Society of America, and Society for Healthcare Epidemiology of America